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The ocean engine of NEMO is a primitive equation model adapted to regional and global ocean circulation problems. It is intended to be a flexible tool for studying the ocean and its interactions with the others components of the earth climate system over a wide range of space and time scales. To cite this edition: Madec, G. and the NEMO System Team, 2023.NEMO Ocean Engine Reference Manual, Zenodo, https://doi.org/10.5281/zenodo.8167700

Interacting many-body quantum systems and their dynamics, while fundamental to modern science and technology, are formidable to simulate and understand. However, by discovering their symmetries, conservation laws, and integrability one can unravel their intricacies. Here, using up to 124 qubits of a fully programmable quantum computer, we uncover local conservation laws and integrability in one- and two-dimensional periodically-driven spin lattices in a regime previously inaccessible to such detailed analysis. We focus on the paradigmatic example of disorder-induced ergodicity breaking, where we first benchmark the system crossover into a localized regime through anomalies in the one-particle-density-matrix spectrum and other hallmark signatures. We then demonstrate that this regime stems from hidden local integrals of motion by faithfully reconstructing their quantum operators, thus providing a detailed portrait of the system's integrable dynamics. Our results demonstrate a versatile strategy for extracting hidden dynamical structure from noisy experiments on large-scale quantum computers., 8 pages, 4 figures (main text) + 19 pages, 17 figures (supplementary)

BACKGROUND: Coronavirus disease 2019 (COVID-19) immediately impacted patient–clinician communication, particularly in the oncology setting. Relatedly, secure messaging (SM) usage greatly increased, yet it is unknown what was discussed and whether the technology was utilized to disseminate information. AIMS: This study aimed at identifying the most frequently discussed topics using SM as well as at understanding how the communication process transpired during the early stages of the pandemic. MATERIALS AND METHODS: A mixed-methods design was utilized, consisting of a content analysis of more than 4,200 secure messages, aggregated into 1,454 patient–clinician discussions. Data were collected from February 2020 to May 2020. Discussions were from various oncology departments and included physicians, physician assistants, and nurses. Based on the identified categories, a thematic analysis was conducted to understand the nuances occurring within discussions. RESULTS: Out of the 1,454 discussions, 26% (n = 373) related to COVID-19. Of the COVID-19 discussion, the most frequently coded category was “changes, adjustments, and re-arranging care” (65%, n = 241), followed by “risk for COVID-19” (24%, n = 90), “precautions inside the hospital” (18%, n = 66), and “precautions outside the hospital” (14%, n = 52). Natural language processing techniques were used to confirm the validity of the results. Thematic analysis revealed that patients were proactive in rescheduling appointments, expressed anxiety about being immunocompromised, and clinicians were uncertain about providing recommendations related to COVID-19. CONCLUSIONS: The COVID-19 outbreak revealed the need for responsive and effective public health communication. The SM can disseminate information from trusted sources, clinicians, but can be better utilized to deliver tailored information for specific patient populations.

We present an analysis of the evolution of near-bed oxygen in the next century in the Northwest European Continental Shelf in a three-member ensemble of coupled physics-biogeochemistry models. The comparison between model results helps highlighting the biogeochemical mechanisms responsible for the observed deoxygenation trends and their response to climate drivers. While all models predict a decrease in near bed oxygen proportional to climate change intensity, the response is spatially heterogeneous, with hotspots of oxygen decline in the members with the most intense change, as well as areas where compensating mechanisms mitigate change. We separate the components of oxygen change associated to the warming effect on oxygen solubility from those due to the effects of changes in transport and ecosystem processes. We find that while warming is responsible for a mostly uniform decline throughout the shelf, changes in transport and ecosystem processes account for the detected heterogeneity. Hotspots of deoxygenation are associated with enhanced stratification that greatly reduces vertical transport. A major change in circulation in the North Sea is responsible for the onset of one such hotspot in the members characterised by intense climate change. Conversely, relatively shallow and well mixed coastal areas in the south experience an increase in net primary production that partially mitigates oxygen decline in all members. This work represents the first multi-model comparison addressing deoxygenation in the Northwest European Shelf and contributes to the understanding of the processes that drive deoxygenation in continental shelf ecosystems.

Digitale Gesundheitsanwendungen (DiGA) können von Ärzten und Psychotherapeuten verschrieben werden. Dazu müssen eine Reihe von Anforderungen erfüllt sein, insbesondere die Zertifizierung als Medizinprodukt und die Aufnahme in das DiGA-Verzeichnis. Dabei werden auch Anforderungen an den Datenschutz gestellt. Die Erklärung des DiGA-Herstellers, dass die Anforderungen an den Datenschutz erfüllt wurden, wird ab Mitte 2024 auf ein Zertifizierungsverfahren umgestellt. Durch die entsprechenden Prüfkriterien des Bundesinstituts für Arzneimittel und Medizinprodukte erfährt das Prüfverfahren eine detailgenauere Standardisierung.

Background Photoplethysmography (PPG) sensors, typically found in wrist-worn devices, can continuously monitor heart rate (HR) in large populations in real-world settings. Resting heart rate (RHR) is an important biomarker of morbidities and mortality, but no universally accepted definition nor measurement criteria exist. In this study, we provide a working definition of RHR and describe a method for accurate measurement of this biomarker, recorded using PPG derived from wristband measurement across the 24-hour cycle. Methods 433 healthy subjects wore a wrist device that measured activity and HR for up to 3 months. HR during inactivity was recorded and the duration of inactivity needed for HR to stabilise was ascertained. We identified the lowest HR during each 24-hour cycle (true RHR) and examined the time of day or night this occurred. The variation of HR during inactivity through the 24-hour cycle was also assessed. The sample was also subdivided according to daily activity levels for subset analysis. Findings Adequate data was obtained for 19,242 days and 18,520 nights. HR stabilised in most subjects after 4 minutes of inactivity. Mean (SD) RHR for the sample was 54.5 (8.0) bpm (day) and 50.5 (7.6) bpm (night). RHR values were highest in the least active group (lowest MET quartile). A circadian variation of HR during inactivity was confirmed, with the lowest values being between 0300 and 0700 hours for most subjects. Interpretation RHR measured using a PPG-based wrist-worn device is significantly lower at night than in the day, and a circadian rhythm of HR during inactivity was confirmed. Since RHR is such an important health metric, clarity on the definition and measurement methodology used is important. For most subjects, a minimum rest time of 4 minutes provides a reliable measurement of HR during inactivity and true RHR in a 24-hour cycle is best measured between 0300 and 0700 hours. Funding: This study was funded by Google.

Fumarate hydratase (FH) is a mitochondrial enzyme that catalyzes the reversible hydration of fumarate to malate in the tricarboxylic acid (TCA) cycle. Germline mutations of FH lead to hereditary leiomyomatosis and renal cell carcinoma (HLRCC), a cancer syndrome characterized by a highly aggressive form of renal cancer. Although HLRCC tumors metastasize rapidly, FH-deficient mice develop premalignant cysts in the kidneys, rather than carcinomas. How Fh1-deficient cells overcome these tumor-suppressive events during transformation is unknown. Here, we perform a genome-wide CRISPR-Cas9 screen to identify genes that, when ablated, enhance the proliferation of Fh1-deficient cells. We found that the depletion of the histone cell cycle regulator (HIRA) enhances proliferation and invasion of Fh1-deficient cells in vitro and in vivo. Mechanistically, Hira loss activates MYC and its target genes, increasing nucleotide metabolism specifically in Fh1-deficient cells, independent of its histone chaperone activity. These results are instrumental for understanding mechanisms of tumorigenesis in HLRCC and the development of targeted treatments for patients.